Project Summary Mind and body approaches, specifically diaphragmatic breathing, progressive muscle relaxation, guided imagery, and biofeedback, improve outcomes for children and adolescents with chronic pain. One prevalent cause of chronic pain is migraine. Worldwide, it is the 2nd most disabling neurological disease. When youth learn and practice mind and body skills, the number of headache days and associated disability are reduced. Typically, trials have tested non-pharmacological intervention packages taught by psychologists, in face-to-face sessions, occurring over 4 to 8 weekly meetings. While efficacious, this model is not accessible to most families because of lack of trained providers, distance and travel barriers, and time commitment to sessions. Our recent pilot studies (both stakeholder engagement and health care provider skills training projects) show that youth who receive outpatient psychological care report that learning breathing, muscle relaxation, guided imagery, and biofeedback are the most useful and impactful components of the larger treatment package. Also, nurses in headache centers report that they would feel comfortable with and are interested in learning how to introduce these skills to patients; and pediatric headache specialists and primary care providers are searching for efficient and effective ways to introduce mind and body skills to their patients. Thus, we need to conduct pragmatic trials to test the delivery of these integrated approaches within the context of typical medical care to confirm if they can provide benefit or not. But, despite evidence of safety, efficacy, and successful prior trial execution, it is necessary to optimize a treatment package by evaluating which components and doses of a complex intervention are critical for changes in outcomes prior to implementing a multi-site effectiveness trial. In this NCCIH U01, we will optimize a migraine prevention treatment package focused on 4 mind and body skills that will be delivered by health care providers (for this project, nurses) in two outpatient headache centers (Cincinnati & Denver). An innovative intervention refinement approach, The Multiphase Optimization Strategy (MOST) (https://methodology.psu.edu/ra/most) will be employed to determine necessary components and doses of an efficient, effective treatment that can then be tested against standard care (patient education without any skills ? training) via a pragmatic trial. For this factorial experiment, we will enroll 200 youth ages 10 to 17 years with a diagnosis of migraine who are experiencing 4 headache days per month (N = 25 per each of 8 conditions). Three components will be tested: session time with nurses for introduction to the skills (dose of 20 or 40 minutes); daily home practice of skills for 8 weeks (dose of a simple handout approach or use of an active, guided eHealth application); and adherence prompt phone call at 1-month (dose of a call or no call). The endpoints are headache days and migraine-related disability (plus treatment fidelity, feasibility, drop-out rates, acceptance, & credibility; sleep; depression; anxiety; and functional disability). The most efficient combination of doses of the 3 components will be determined using the MOST approach, guided by the resource management and the optimization principles.